Walter, Georg and Liebl, Renate and von Angerer, Erwin (2004) Stilbene-based inhibitors of estrone sulfatase with a dual mode of action in human breast cancer cells. ARCHIV DER PHARMAZIE, 337 (12). pp. 634-644. ISSN 0365-6233, 1521-4184
Full text not available from this repository. (Request a copy)Abstract
Estrone sulfate (E1S) is an endogenous prodrug that delivers estrone and, subsequently, estradiol to target cells, after hydrolysis by the enzyme estrone sulfatase, which is active in various tissues including hormone-dependent breast cancer. Blockade of this enzyme should reduce the estrogen level in breast cancer cells and prevent hormonal growth stimulation. In this study, a number of sulfamoyloxy-substituted stilbenes with side chains that guarantee antiestrogenic activity were synthesized and evaluated as inhibitors of estrone sulfatase. They inhibited this enzyme in human MDA-MB 231 breast cancer cells, with IC50 values in the submicromolar range. The effects of both the free hydroxy derivatives and the sulfamates on gene activation were determined in transfected MCF-7/2a breast cancer cells stimulated either with estradiol or with estrone sulfate. The analysis of data revealed a dual mode of action of the majority of compounds. They blocked gene expression by inhibition of estrone sulfatase and by antiestrogenic action. This pharmacological profile was also observed in assays on anti proliferative activity. The most potent derivative 8g inhibited the growth of wild-type human MCF-7 cells with an IC50 value of 13 nM.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | HUMAN STEROID SULFATASE; POTENT INHIBITORS; AROMATASE ACTIVITIES; EXPRESSION; 2-PHENYLINDOLES; ESTRADIOL; ANALOGS; stilbene sulfamates; steroid sulfatase; antiestrogen; breast cancer cells |
| Subjects: | 600 Technology > 615 Pharmacy |
| Divisions: | Chemistry and Pharmacy > Institute of Pharmacy > Alumni or Retired Professors > Pharmaceutical/Medicinal Chemistry II (Prof. Buschauer) |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 21 Jun 2021 09:59 |
| Last Modified: | 21 Jun 2021 09:59 |
| URI: | https://pred.uni-regensburg.de/id/eprint/36879 |
Actions (login required)
 |
View Item |
